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Abstract

Background: Brain aging is a multi-factorial process due to both genetic and environmental factors. The zebrafish
has recently become a popular model organism for examining aging and age-related diseases because as in
humans they age gradually and exhibit cognitive decline. Few studies have examined the biological changes in the
aging brain that may contribute to these declines and none have examined them within individuals with respect to
gender. Our aim was to identify the main genetic pathways associated with zebrafish brain aging across gender. We
chose males and females from specific age groups (young, 7.5-8.5 months and old, 31-36 months) based on the
progression of cognitive decline in zebrafish. RNA was isolated from individual brains and subjected to microarray and
qPCR analysis. Statistical analyses were performed using a two-way ANOVA and the relevant post-hoc tests.
Results: Our results demonstrated that in the brains of young and old male and female zebrafish there were over 500
differentially expressed genes associated with multiple pathways but most notably were those related to neurogenesis
and cell differentiation, as well as brain and nervous system development.
Conclusions: The gene expression of multiple pathways is altered with age and differentially expressed in males and
females. Future studies will be aimed at determining the causal relationships of age-related changes in gene expression
in individual male and female brains, as well as possible interventions that counteract these alterations.